The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients.

Abstract

BACKGROUND: Tumor-associated macrophages (TAMs) have varying functions depending on the microenvironment of tumor tissue. We studied the biological role of TAMs in gastric cancer on the basis of their spatial distribution in the cancer tissue. MATERIALS AND METHODS: Tissue specimens from 84 advanced gastric carcinoma (pT2; 41 cases, pT3; 43 cases) patients who had undergone a curative resection were stained for TAM (CD68+ cells), incidence of tumor cell apoptosis (TUNEL) and host immune status (CD8+ T cells). CD68+ and CD8+ T cells infiltrated into the cancer cell nests or in close contact with cancer cells were considered as nest TAMs and nest CD8, respectively. RESULTS: Nest TAMs had a very strong direct correlation with frequency of tumor cell apoptosis (p < 0.0001) and degree of nest CD8 (p = 0.0004). The 5-year disease-free survival rate in the high-nest TAM category (87%) was significantly higher than in the low-nest TAM group (44%) (p = 0.0002). Among the several prognostic factors, nest TAM, nest CD8 and pT stage became independent predictors of patient survival (p = 0.016, p = 0.001 and p = 0.029, respectively) in Cox's multivariate analysis. CONCLUSION: These results suggested that the aggregation of TAMs within tumor nest had a beneficial effect on host in terms of augmented cytotoxicity and antigen presentation.